Wednesday, May 3, 2006

Bird Flu Blues: Science Reports on The State of Our Ignorance

Science published an issue on April 21st about influenza: anyone interested in bird flu should look it up.  The table of contents, a summary of the issue's contents, and the contents of Science's special access portal can be found below. 

  Here's the table of contents:

Science Influenza Special Issue:  21 April 2006


Early Diagnosis of Avian Influenza >
Peter S. Lu


Influenza: The State of Our Ignorance >
C. Ash and L. Roberts


A One-Size-Fits-All Flu Vaccine? >
J. Kaiser
Oseltamivir Becomes Plentiful -- But Still Not Cheap >
M. Enserink



Emergence of Drug-Resistant Influenza Virus: Population Dynamical Considerations >
R. R. Regoes and S. Bonhoeffer
Predictability and Preparedness in Influenza Control >
D. J. Smith
Host Species Barriers to Influenza Virus Infections >
T. Kuiken, E. C. Holmes, J. McCauley, G. F. Rimmelzwaan, C. S. Williams, and B. T. Grenfell



Global Patterns of Influenza A Virus in Wild Birds >
B. Olsen, V. J. Munster, A. Wallensten, J. Waldenström, A. D. M. E. Osterhaus, and R. A. M. Fouchier



H5N1 Virus Attachment to Lower Respiratory Tract >
D. van Riel et al.
Avian influenza H5N1 attaches most efficiently to cell types located deep in the lungs of some mammals, influencing pathology and transmissibility.
Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus >
J. Stevens et al.
A surface protein on the "bird flu" virus binds avian cells and with a few mutations could allow more avid attachment to human cells, facilitating infection.
Synchrony, Waves, and Spatial Hierarchies in the Spread of Influenza >
C. Viboud et al.
Thirty years of data indicate that in the United States, seasonal flu epidemics often spread by adult-to-adult transfer during commuting on public transportation.

On the Science Podcast

This week's entire show is devoted to influenza -- including interviews with Science news contributors Martin Enserink and Jocelyn Kaiser on Tamiflu and universal flu vaccines, and with scientists Ron Fouchier on wild birds as carriers of influenza, Angus Nicoll on outbreak responses, and Jeffrey Taubenberger on what we can learn from studying the 1918 pandemic flu virus.

Here's part of the summary of the April 21, 2006 issue written by Caroline Ash and Leslie Roberts.  Link: Science.

Olsen and colleagues (p. 384) outline the unseen network of influenza among migratory birds that spans Earth. H5N1 has engendered alarm not only because it is unusually virulent, laying waste to poultry and causing severe economic losses for farmers, but also because it can, with some difficulty, infect humans and other mammals. So far, the virus has killed more than half of the nearly 200 people known to have been infected. Kuiken and colleagues (p. 394) explore the routes through the obstacles to interspecies transmission (the host species barrier) of viruses. Their analysis focuses on which adaptations are needed to facilitate bird-to-human transfer of H5N1. Examples are provided by Shinya* and in a Brevia by van Riel et al. (p. 399). These authors show that the virus preferentially binds to cell types bearing specific surface receptors found deep in the lungs, which may partly explain its poor human-to-human transmissibility.

The combination of ever-unfolding modes of variability (Stevens, p. 404) and symptomless transmission makes identification of the virus slow and hinders the implementation of influenza containment. As Lu outlines in his Editorial (p. 337), we urgently need faster and more robust diagnostic tests for field use (an area we will be covering shortly in our pages). Further articles in this special section describe other tools and approaches for preparedness. Smith (p. 392) summarizes the models that have been developed for tracing the rate and spread of pandemic influenza through human populations, including scenarios for the deployment of drugs and development of vaccines. We might be able to buy some time for vaccine manufacture by stockpiling antiviral drugs for immediate use, but that time may be short. Regoes and Bonhoeffer (p. 389) indicate that the generation and transmission of resistant strains could happen quickly. Unfortunately, our knowledge of influenza transmission is incomplete, and more basic data are needed to make models accurate and to give them predictive weight. Seasonal influenza statistics will provide an important insight into the transmission biology of influenza; Viboud et al. (p. 447) have used a large data set from the United States to model annual waves of infection.

In a News story (p. 380), Kaiser explores efforts to develop broader influenza vaccines that protect against new strains and perhaps even all influenza subtypes. Antiviral drugs are also sorely needed to fight a pandemic, but oseltamivir, or Tamiflu, has been in short supply. As Enserink describes (p. 382), Roche and other companies are now ramping up production, while scientists are investigating faster and cheaper synthetic pathways that could make the drug affordable to developing countries.


Anyone researching bird flu should consider subscribing, if only for access to Science's special portal.  That portal includes:



Combating the Bird Flu Menace, Down on the Farm >
Richard Stone
Science 311,  944  (17 February 2006)
Pandemic Skeptics Warn Against Crying Wolf >
Dennis Normile
Science 310,  1112  (18 November 2005)
Are Wild Birds to Blame? >
Dennis Normile
Science 310,  426  (21 October 2005)
Drugs, Quarantine Might Stop a Pandemic Before It Starts >
Martin Enserink
Science 309,  870  (5 August 2005)
Who Controls the Samples? >
Dennis Normile
Science 309,  372  (15 July 2005)
True Numbers Remain Elusive in Bird Flu Outbreak >
Martin Enserink and Dennis Normile
Science 307,  1865  (25 March 2005)
Looking the Pandemic in the Eye >
Martin Enserink
Science 306,  392  (15 October 2004)
Facing Down Pandemic Flu, the World's Defenses Are Weak >
Jocelyn Kaiser
Science 306,  394  (15 October 2004)
Asia Struggles to Keep Humans and Chickens Apart >
Dennis Normile
Science 306,  399  (15 October 2004)
Tiptoeing Around Pandora's Box >
Martin Enserink
Science 305,  594  (30 July 2004)


Community Studies for Vaccinating Schoolchildren Against Influenza >
M. Elizabeth Halloran and Ira M. Longini Jr.
Science 311,  615  (3 February 2006)
Will Vaccines Be Available for the Next Influenza Pandemic? >
Klaus Stöhr and Marja Esveld
Science 306,  2195  (24 December 2004)
Public Health Risk from the Avian H5N1 Influenza Epidemic >
Neil M. Ferguson, Christophe Fraser, Christl A. Donnelly, Azra C. Ghani, and Roy M. Anderson
Science 304,  968 (14 May 2004)


Are We Ready for Pandemic Influenza? >
Richard J. Webby and Robert G. Webster
Science 302,  1519  (28 November 2003)




Clues to the Virulence of H5N1 Viruses in Humans >
Robert M. Krug
Science 311,  1562  (17 March 2006)
1918 and All That >
Edward C. Holmes
Science 303,  1787  (19 March 2004)
The Origin and Control of Pandemic Influenza >
Graeme Laver and Elspeth Garman
Science 293,  1776 (7 September 2001)
A Molecular Whodunit >
Robert G. Webster
Science 293,  1773 (7 September 2001)


Large-Scale Sequence Analysis of Avian Influenza Isolates >
John C. Obenauer et al.
Science 311,  1576  (17 March 2006)
Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus >
Terrence M. Tumpey et al.
Science 310,  77  (7 October 2005)
Highly Pathogenic H5N1 Influenza Virus Infection in Migratory Birds >
J. Liu et al.
Science 309,  1206  (19 August 2005)
Containing Pandemic Influenza at the Source >
Ira M. Longini, Jr., et al.
Science 309,  1083  (3 August 2005)
Avian H5N1 Influenza in Cats >
Thijs Kuiken et al.
Science 306,  241  (8 October 2004)
Mapping the Antigenic and Genetic Evolution of Influenza Virus >
Derek J. Smith et al.
Science 305,  371  (24 June 2004)
The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin  >
S. J. Gamblin  et al.
Science 303,  1838  (19 March 2004)
Structure of the Uncleaved Human H1 Hemagglutinin from the Extinct 1918 Influenza Virus >
James Stevens et al.
Science 303,  1866  (19 March 2004)
Recombination in the Hemagglutinin Gene of the 1918 "Spanish Flu" >
Mark J. Gibbs, John S. Armstrong,  Adrian J. Gibbs
Science 293,  1842 (7 September 2001)
Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses >
Masato Hatta, Peng Gao, Peter Halfmann, and Yoshihiro Kawaoka
Science 293,  1840 (7 September 2001)



In Science Classic:  The 1918 Pandemic



The Influenza Pneumonia Pandemic in the American Army Camps during September and October, 1918 [PDF] >
George A. Soper
Science 48,  451  (8 November 1918)
Statistical Study of the Influenza Epidemic [PDF] >
Edwin W. Kopf
Science 49,  228  (7 March 1919)


The Lessons of the Pandemic [PDF] >
George A. Soper
Science 49,  501  (30 May 1919)

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